Super-enhancer-driven ameboidal-type cell migration-related MMP14 expression in tongue squamous cell carcinoma switched by BATF and ATF3.

IF 2.8 4区医学 Q2 PHARMACOLOGY & PHARMACY

Journal of Pharmacy and Pharmacology Pub Date : 2025-01-06 DOI:10.1093/jpp/rgae063

Zhimin Shi, Rui Wang, Jie Huang, Qian Qian, Menglin Hu, Hengguo Zhang, Linfei Feng, Hao Gu, Yuanyin Wang

{"title":"Super-enhancer-driven ameboidal-type cell migration-related MMP14 expression in tongue squamous cell carcinoma switched by BATF and ATF3.","authors":"Zhimin Shi, Rui Wang, Jie Huang, Qian Qian, Menglin Hu, Hengguo Zhang, Linfei Feng, Hao Gu, Yuanyin Wang","doi":"10.1093/jpp/rgae063","DOIUrl":null,"url":null,"abstract":"Background: Tongue squamous cell carcinoma (TSCC) exhibits an aggressive biological behavior of lymph node and distant metastasis, which contributes to poorer prognosis and results in tongue function loss or death. In addition to known regulators and pathways of cell migration in TSCC, it is important to uncover pivotal switches governing tumor metastasis.Methods: Cancer cell migration-associated transcriptional and epigenetic characteristics were profiled in TSCC, and the specific super-enhancers (SEs) were identified. Molecular function and mechanism studies were used to investigate the pivotal switches in TSCC metastasis.Results: Ameboidal-type cell migration-related genes accompanied by transcriptional and epigenetic activity were enriched in TSCC. Meanwhile, the higher-ranked SE-related genes showed significant differences between 43 paired tumor and normal samples from the TCGA TSCC cohort. In addition, key motifs were detected in SE regions, and transcription factor-related expression levels were significantly associated with TSCC survival status. Notably, BATF and ATF3 regulated the expression of ameboidal-type cell migration-related MMP14 by switching the interaction with the SE region.Conclusion: SEs and related key motifs transcriptional regulate tumor metastasis-associated MMP14 and might be potential therapeutic targets for TSCC.","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":" ","pages":"64-75"},"PeriodicalIF":2.8000,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Pharmacy and Pharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/jpp/rgae063","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}

引用次数: 0

Abstract

Background: Tongue squamous cell carcinoma (TSCC) exhibits an aggressive biological behavior of lymph node and distant metastasis, which contributes to poorer prognosis and results in tongue function loss or death. In addition to known regulators and pathways of cell migration in TSCC, it is important to uncover pivotal switches governing tumor metastasis.

Methods: Cancer cell migration-associated transcriptional and epigenetic characteristics were profiled in TSCC, and the specific super-enhancers (SEs) were identified. Molecular function and mechanism studies were used to investigate the pivotal switches in TSCC metastasis.

Results: Ameboidal-type cell migration-related genes accompanied by transcriptional and epigenetic activity were enriched in TSCC. Meanwhile, the higher-ranked SE-related genes showed significant differences between 43 paired tumor and normal samples from the TCGA TSCC cohort. In addition, key motifs were detected in SE regions, and transcription factor-related expression levels were significantly associated with TSCC survival status. Notably, BATF and ATF3 regulated the expression of ameboidal-type cell migration-related MMP14 by switching the interaction with the SE region.

Conclusion: SEs and related key motifs transcriptional regulate tumor metastasis-associated MMP14 and might be potential therapeutic targets for TSCC.

查看原文本刊更多论文

舌鳞状细胞癌中由BATF和ATF3切换的超级增强子驱动的meboidal型细胞迁移相关的MMP14表达。

背景：舌鳞状细胞癌（TSCC）具有淋巴结和远处转移的侵袭性生物学行为，导致预后较差，并导致舌功能丧失或死亡。除了已知的TSCC细胞迁移调控因子和途径外，揭示肿瘤转移的关键开关也很重要：方法：分析了TSCC中与癌细胞迁移相关的转录和表观遗传学特征，并确定了特异性超级增强子（SEs）。方法：分析了TSCC中与癌细胞迁移相关的转录和表观遗传学特征，并确定了特异性超级增强子（SEs），利用分子功能和机制研究探讨了TSCC转移过程中的关键开关：结果：TSCC中富集了伴随转录和表观遗传活性的淀粉样细胞迁移相关基因。同时，排名较高的SE相关基因在TCGA TSCC队列的43个配对肿瘤样本和正常样本中显示出显著差异。此外，在SE区域还检测到了关键基因，转录因子相关的表达水平与TSCC的存活状况有显著相关性。值得注意的是，BATF和ATF3通过切换与SE区域的相互作用来调节与无畸形细胞迁移相关的MMP14的表达：结论：SEs及相关关键基团转录调控肿瘤转移相关的MMP14，可能是TSCC的潜在治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Journal of Pharmacy and Pharmacology 医学-药学

CiteScore

6.60

自引率

0.00%

发文量

审稿时长

3 months

期刊介绍： JPP keeps pace with new research on how drug action may be optimized by new technologies, and attention is given to understanding and improving drug interactions in the body. At the same time, the journal maintains its established and well-respected core strengths in areas such as pharmaceutics and drug delivery, experimental and clinical pharmacology, biopharmaceutics and drug disposition, and drugs from natural sources. JPP publishes at least one special issue on a topical theme each year.